Andrau Jean-Christophe, van de Pasch Loes, Lijnzaad Philip, Bijma Theo, Koerkamp Marian Groot, van de Peppel Jeroen, Werner Michel, Holstege Frank C P
Department of Physiological Chemistry, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Mol Cell. 2006 Apr 21;22(2):179-92. doi: 10.1016/j.molcel.2006.03.023.
Mediator is a general coactivator of RNA polymerase II (Pol II) transcription. Genomic location analyses of different Mediator subunits indicate a uniformly composed core complex upstream of active genes but unexpectedly also upstream of inactive genes and on the coding regions of some highly active genes. The repressive Cdk8 submodule is associated with core Mediator at all sites but with a lower degree of occupancy, indicating transient interaction, regardless of promoter activity. This suggests gene-specific regulation of Cdk8 activity, rather than regulated Cdk8 recruitment. Mediator presence is not necessarily linked to transcription. This goes beyond Cdk8-repressed genes, indicating that Mediator can mark some regulatory regions ahead of additional signals. Overlap with intergenic Pol II location in stationary phase points to a role as a binding platform for inactive Pol II during quiescence. These results shed light on Cdk8 repression, suggest additional roles for Mediator, and query models of recruitment-coupled regulation.
中介体是RNA聚合酶II（Pol II）转录的一种通用共激活因子。对不同中介体亚基的基因组定位分析表明，在活跃基因上游存在一个组成均匀的核心复合物，但出乎意料的是，在非活跃基因上游以及一些高活性基因的编码区域也存在。抑制性的Cdk8亚模块在所有位点都与核心中介体相关联，但占据程度较低，表明存在瞬时相互作用，与启动子活性无关。这表明Cdk8活性存在基因特异性调控，而非Cdk8招募受到调控。中介体的存在不一定与转录相关。这一现象不仅限于Cdk8抑制的基因，表明中介体可以在其他信号之前标记一些调控区域。在静止期与基因间Pol II定位的重叠表明，中介体在静止期间作为非活性Pol II的结合平台发挥作用。这些结果揭示了Cdk8的抑制作用，暗示了中介体的其他作用，并对招募偶联调控模型提出了质疑。
